DESCRIPTION: The objective of this work is to develop a base of information about the effects of caffeine on cardiovascular and neuroendocrine functions during rest and during mental and exercise stressors. Caffeine is widely used in pharmacologically significant quantities. It affects the central nervous system, cardiovascular activity, and neuroendocrine function. Consumption may increase during times of mental stress, and it is often present during exercise. Caffeine has been shown to increase cardiovascular disease risk factors such as serum cholesterol and lipid fractions. However, the potential effects of caffeine may be reduced by development of tolerance in habitual users. The goal of this project is to examine whether caffeine's elevation of blood pressure (BP) and cortisol (CORT) is smaller following regular intake. Understanding this reduction of effect is essential to properly evaluate caffeine's physiological effects and potential consequences for health. In view of public concerns about caffeine use and reports of negative health consequences, it is important to have a well established body of information about caffeine's effects and their modification by tolerance in humans. Tolerance will be tested by varying levels of intake from 0 to 600 mg/day (equivalent to 6 cups of coffee) in 128 volunteers over 4 weeks and examining the resulting modifications of blood pressure and cortisol responses to an acute caffeine dose (3.3 mg/kg). Caffeine's ability to elevate BP and CORT represents two of its most pervasive and important physiological effects, and these will be the model response systems under study. This project has three specific aims: first to study the effect of tolerance on acute (1 hr) BP and CORT responses to a morning challenge dose of caffeine; second to measure the effect of tolerance on BP and CORT responses during acute stress (30 min mental stress or exercise) following the morning challenge dose; and third to examine the effect of tolerance on levels of BP and CORT during a day of ambulatory BP monitoring following a repeated challenge dose. The primary hypothesis is that regular intake of caffeine produces a partial tolerance to its effects, and that this may vary substantially from person to person. This information will help us to properly evaluate in context the evidence showing that caffeine can alter physiological functions and responses to stress.